It is proposed to study detoxication mechanisms in insects using the housefly and related Diptera. The research will concentrate on three areas: the biochemical properties of the microsomal oxidases and other detoxifying enzymes; the regulation of these enzymes; and the genetic inheritance of metabolic factors involved in resistance to insecticides. We will attempt to fractionate housefly microsomes into a cytochrome P-450, a cytochrome P-450 reductase, and a lipid fraction as has already been done with hepatic microsomes. The properties of these fractions will be studied with respect to their metabolism of pesticides and other biologically active compounds. Comparisons will be made of fractions prepared from genetically characterized housefly strains. The induction of detoxifying enzymes by exogenous chemicals and by insect hormones and the role of this induction in the metabolism of these hormones will be an important part of the proposed work. A cell line established from housefly embryonic tissue will be used to supplement information gathered from the intact insect and from sub-cell fractions. Other approaches to the study of induction will include the study of P-450 synthesis during induction and the measure of induction in individuals from a population. The five housefly chromosomes will be manipulated in a variety of resistant, susceptible, and mutant marker strains, in order to isolate the individual factors responsible for insecticide resistance. Special substrains, selected for high levels of detoxifying enzyme activity, will be studied genetically and biochemically.